Our sense of smell can help protect us from spoiled foods, environmental hazards such as gas leaks or smoke, and provide a rich background to our daily lives. However, the mechanisms underlying the processing and coding of olfactory information in the brain are unclear. Odor information is first encoded in the spiking of olfactory sensory neurons, which in turn synapse in the olfactory bulb. Previous studies have demonstrated experience and context dependent changes in the activity of olfactory bulbar neurons, which may allow animals to better encode particularly salient odor information. Cortical feedback projections from the olfactory cortex to the olfactory bulb are poised to mediate the top-down regulation of olfactory bulb activity during these behavioral conditions. Despite their potential impact on early sensory processing, the targets and basic properties of these cortical feedback projections still remain largely unknown. Where do cortical feedback projections synapse, and how to they affect the activity of mitral/tufted cells, the output neurons of the bulb In this proposal, we will address these questions using an optogenetic approach. Viral expression of channelrhodopsin (ChR2) in layer 2/3 pyramidal cells of olfactory cortex will be used to selectively and acutely activate pyramidal cell axons in mouse olfactory bulb slices. Using cell-attached and whole-cell patch clamp recording, we will examine ChR2 evoked responses in postsynaptic targets of cortical feedback projections. This study has 2 specific aims: Aim 1: Characterize the postsynaptic targets of cortical feedback projections and Aim 2: Determine the effects of cortical feedback on mitral and tufted cell output. PUBLIC HEALTH RELEVANCE: A major goal in neuroscience is to understand how the brain encodes the sensory information that allows us to perceive and interact with our environment. Ultimately, determining how cortical feedback influences olfactory bulb circuits will yield a bette understanding of how cortical areas can influence early sensory transduction in a behaviorally beneficial manner. Cortical feedback is a universal feature of all sensory systems and thus likely represents an important general strategy for optimizing sensory information processing.